This research is very unique. First it focuses on developing an anti-malarial compound which is based on a library of similar probable compounds that were discovered by Find-A-Drug. Developing a new anti-malarial through a chemistry research laboratory is challenging in itself, but it questionable as there are other anti-malarial drugs on the market that do a half decent job. The purpose therefore of this aspect of this research is to make a better anti-malarial. The reason for this is due to the powerful resistivity of the protozoan parasites that are classified into four species which cause malaria. The genus that all of the parasites have in common is called plasmodium and the four species are falciparum, vivax, ovale, and malaria. The compounds of this library are 1,4-diketopiperazines and using software which mimics a bonding capabilities of compounds particularly complex protein structures these compounds were found to be good inhibitors to a particular enzyme found in malaria, enoyl reductase. The enoyl-acyl carrier protein reductase (ENR) is involved in bacterial fatty acid biosynthesis. It is believed that the inhibition of this protein would terminate the parasite’s ability to survive in the human blood stream. While it not a vaccine the compound may be a better substitute to some of the other anti-malarial drugs on the market.
Through a literature search, a one pot multi-component reaction was found to synthesize a starting compound. This reaction is the Ugi reaction which combines a protected amino acid, an aldehyde, an amine, and an isocyanide. These compounds were mixed in methanol and allowed to react for 24 hours. After this, the methanol would be evaporated and then the Ugi product would be treated with 10% TFA in 1,2 dichloroethane. The result according to Hulme et al is a cyclization of the Ugi product into a 1,4-diketopiperazine. The particular groups attached to the piperazine ring varied based on the structure of each diketopiperazine in the library. In practice the cyclization always failed. The work there after and in this paper focuses on the making of DOPAL, a Ugi product as a step wise reaction which reveals a reversal of imine formation after addition of the acid.
Another major facet of this research revolves around it being an Open Source research project. This open source project is generally defined as a free reference to all of our experiments, success or failure, that anyone, scientist or not, can comment on.
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